JP5004236B2 - Orally disintegrating tablets - Google Patents
Orally disintegrating tablets Download PDFInfo
- Publication number
- JP5004236B2 JP5004236B2 JP2007502589A JP2007502589A JP5004236B2 JP 5004236 B2 JP5004236 B2 JP 5004236B2 JP 2007502589 A JP2007502589 A JP 2007502589A JP 2007502589 A JP2007502589 A JP 2007502589A JP 5004236 B2 JP5004236 B2 JP 5004236B2
- Authority
- JP
- Japan
- Prior art keywords
- weight
- manufactured
- pregelatinized starch
- cold water
- partially pregelatinized
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims description 73
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 127
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 114
- 229920000881 Modified starch Polymers 0.000 claims description 107
- 239000003826 tablet Substances 0.000 claims description 76
- 235000010355 mannitol Nutrition 0.000 claims description 50
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 45
- 229960000913 crospovidone Drugs 0.000 claims description 45
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 45
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 45
- 239000004480 active ingredient Substances 0.000 claims description 32
- 239000007884 disintegrant Substances 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 23
- 238000002156 mixing Methods 0.000 claims description 20
- QEVLNUAVAONTEW-UZYHXJQGSA-L calcium;(2s)-4-[(3as,7ar)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzyl-4-oxobutanoate;dihydrate Chemical group O.O.[Ca+2].C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)[O-])C1=CC=CC=C1.C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)[O-])C1=CC=CC=C1 QEVLNUAVAONTEW-UZYHXJQGSA-L 0.000 claims description 14
- 229960003365 mitiglinide Drugs 0.000 claims description 14
- 229920002261 Corn starch Polymers 0.000 claims description 11
- 239000008120 corn starch Substances 0.000 claims description 11
- IOVGROKTTNBUGK-SJKOYZFVSA-N (1S,2R)-ritodrine Chemical group N([C@H](C)[C@@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJKOYZFVSA-N 0.000 claims description 6
- 229960000720 ritodrine hydrochloride Drugs 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- 239000004471 Glycine Substances 0.000 claims 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 74
- 239000000203 mixture Substances 0.000 description 67
- 235000019359 magnesium stearate Nutrition 0.000 description 37
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 37
- 235000012239 silicon dioxide Nutrition 0.000 description 37
- 150000005846 sugar alcohols Chemical class 0.000 description 33
- 235000000346 sugar Nutrition 0.000 description 31
- 238000005469 granulation Methods 0.000 description 30
- 230000003179 granulation Effects 0.000 description 30
- 229920002472 Starch Polymers 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 235000019698 starch Nutrition 0.000 description 24
- 239000000126 substance Substances 0.000 description 21
- 239000002245 particle Substances 0.000 description 20
- 239000008213 purified water Substances 0.000 description 20
- 239000008107 starch Substances 0.000 description 20
- 239000008187 granular material Substances 0.000 description 19
- 238000005507 spraying Methods 0.000 description 19
- 238000000748 compression moulding Methods 0.000 description 18
- 101100288387 Caenorhabditis elegans lab-1 gene Proteins 0.000 description 17
- 239000007921 spray Substances 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- 239000006185 dispersion Substances 0.000 description 15
- 238000013019 agitation Methods 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 12
- 238000012360 testing method Methods 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 210000000214 mouth Anatomy 0.000 description 8
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 229920001353 Dextrin Polymers 0.000 description 5
- 239000004375 Dextrin Substances 0.000 description 5
- 235000019425 dextrin Nutrition 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 108010011485 Aspartame Proteins 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000004088 foaming agent Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000005096 rolling process Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000009747 swallowing Effects 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000005107 Premature Birth Diseases 0.000 description 2
- 206010036590 Premature baby Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000028938 Urination disease Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 229940127003 anti-diabetic drug Drugs 0.000 description 2
- 229940035678 anti-parkinson drug Drugs 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229960004596 cabergoline Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 238000009775 high-speed stirring Methods 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229960004953 silodosin Drugs 0.000 description 2
- PNCPYILNMDWPEY-QGZVFWFLSA-N silodosin Chemical compound N([C@@H](CC=1C=C(C=2N(CCCO)CCC=2C=1)C(N)=O)C)CCOC1=CC=CC=C1OCC(F)(F)F PNCPYILNMDWPEY-QGZVFWFLSA-N 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- -1 that is Substances 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- WLDHEUZGFKACJH-ZRUFZDNISA-K Amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1\N=N\C1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-ZRUFZDNISA-K 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- JLRNKCZRCMIVKA-UHFFFAOYSA-N Simfibrate Chemical compound C=1C=C(Cl)C=CC=1OC(C)(C)C(=O)OCCCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 JLRNKCZRCMIVKA-UHFFFAOYSA-N 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 229950003837 ozagrel Drugs 0.000 description 1
- SHZKQBHERIJWAO-AATRIKPKSA-N ozagrel Chemical compound C1=CC(/C=C/C(=O)O)=CC=C1CN1C=NC=C1 SHZKQBHERIJWAO-AATRIKPKSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 229960004058 simfibrate Drugs 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 1
- 229960005342 tranilast Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 239000003232 water-soluble binding agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Reproductive Health (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、口腔内で速やかに崩壊する錠剤およびその製造方法に関する。 The present invention relates to a tablet that rapidly disintegrates in the oral cavity and a method for producing the same.
近年、高齢者、小児や嚥下困難な患者が服用しやすい剤形、あるいは水なしで服用できる剤形として、口腔内で速やかに崩壊もしくは溶解する固形製剤の開発が進められている。 In recent years, development of solid preparations that rapidly disintegrate or dissolve in the oral cavity has been promoted as dosage forms that can be easily taken by elderly people, children, and patients who have difficulty swallowing, or can be taken without water.
例えば、活性成分の懸濁液を鋳型に分注後、凍結乾燥して調製される口腔内崩壊錠が知られているが（例えば、特許文献１参照）、当該方法では凍結乾燥設備を必要とし、さらに得られる口腔内崩壊錠は、硬度が小さいため取り扱いが不便である。 For example, an orally disintegrating tablet prepared by dispensing a suspension of an active ingredient into a mold and then freeze-drying is known (see, for example, Patent Document 1), but this method requires freeze-drying equipment. Further, the orally disintegrating tablet obtained is inconvenient to handle because of its low hardness.
特開平８−２９１０５１には、活性成分、水溶性結合剤および水溶性賦形剤を含有する造粒物を圧縮成形後、加湿、乾燥して調製される口腔内崩壊錠の製造方法が開示されているが、当該方法では特殊な製造設備が必要とされている（例えば、特許文献２参照）。 Japanese Patent Application Laid-Open No. 8-291051 discloses a method for producing an orally disintegrating tablet prepared by compression-molding a granulated product containing an active ingredient, a water-soluble binder and a water-soluble excipient, followed by humidification and drying. However, this method requires special manufacturing equipment (see, for example, Patent Document 2).
ＷＯ９５/２０３８０には、成形性の低い糖類と成形性の高い糖類とを組み合わせて造粒、圧縮成形した後、硬度を高めるため加湿、乾燥して調製される口腔内崩壊製剤が開示されている（例えば、特許文献３参照）。 WO95 / 20380 discloses an orally disintegrating preparation prepared by granulating and compression-molding a combination of a low moldability saccharide and a high moldability saccharide, and then humidifying and drying to increase hardness. (For example, refer to Patent Document 3).
また、賦形剤として成形性の低い糖アルコールまたは糖類と、崩壊剤とを組み合わせてなる様々な口腔内崩壊錠が提案されている。 In addition, various orally disintegrating tablets have been proposed in which a sugar alcohol or saccharide having low moldability as an excipient and a disintegrant are combined.
例えば、ＷＯ９７/４７２８７には、平均粒子径３０μｍ以下の糖アルコールまたは糖類と、活性成分および崩壊剤とを組み合わせてなり、適度な硬度と崩壊性を有する口腔内崩壊錠が開示されている（例えば、特許文献４参照）。しかしながら、ここに用いられているＤ−マンニトールは圧縮成形時に金属壁面との摩擦が大きく、バインディング、キャッピングなどの打錠障害を引き起こす問題があることから、圧縮成形時に、臼杵に滑沢剤を塗布して打錠するなどの特殊な製造設備が必要とされている。 For example, WO97 / 47287 discloses an orally disintegrating tablet comprising a combination of a sugar alcohol or saccharide having an average particle size of 30 μm or less, an active ingredient and a disintegrant, and having appropriate hardness and disintegration (for example, , See Patent Document 4). However, D-mannitol used here has a problem of causing a tableting trouble such as binding and capping due to large friction with the metal wall surface during compression molding, so a lubricant is applied to the mortar during compression molding. Therefore, special manufacturing equipment such as tableting is required.
ＷＯ２０００/５７８５７には、噴霧乾燥したＤ−マンニトールとクロスポビドンとを含有する混合物を直接打錠して調製される、適度な硬度と崩壊性を有する口腔内崩壊錠が開示されている（例えば、特許文献５参照）。また、特開２００１−１６３７７０には、糖類および崩壊剤を含有する混合物の共粉砕物と、糖類の未粉砕物とを含有する打錠用末を直接圧縮してなる、適度な硬度と崩壊性を有する口腔内崩壊錠が開示されている（例えば、特許文献６参照）。しかしながら、賦形剤としてＤ−マンニトールを使用し、これらの方法に従って口腔内崩壊錠を調製した場合、圧縮成形時に、依然としてバインディングなどの打錠障害を生じやすいという課題を有している。
本発明の目的は、適度な硬度と速やかな崩壊性を有し、一般的な製造設備で工業的生産が可能である口腔内崩壊錠を提供することである。 An object of the present invention is to provide an orally disintegrating tablet that has moderate hardness and quick disintegration, and that can be industrially produced by general production equipment.
本発明者らは、上記課題を解決すべく鋭意研究を重ねた結果、活性成分、糖または糖アルコールおよび崩壊剤と、特定の範囲の冷水可溶分を有する部分アルファー化デンプンとを含有する口腔内崩壊錠が、適度な硬度と速やかな崩壊性を有すること、さらには当該口腔内崩壊錠が、予想外にも圧縮成形時における打錠障害を生じることなく一般的な製造設備で容易に生産できることを見出し、これらの知見に基づき、本発明を完成したものである。 As a result of intensive studies to solve the above problems, the present inventors have found that the oral cavity contains an active ingredient, sugar or sugar alcohol and a disintegrant, and partially pregelatinized starch having a specific range of cold water soluble content. The internally disintegrating tablet has moderate hardness and quick disintegration, and the orally disintegrating tablet is easily produced with ordinary manufacturing equipment without unexpectedly causing tableting troubles during compression molding. Based on these findings, the present invention has been completed.
すなわち、本発明は、
〔１〕 ａ）活性成分、ｂ）糖または糖アルコール、ｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプン、およびｄ）崩壊剤を含有する口腔内崩壊錠；
〔２〕 糖または糖アルコールが、乳糖およびＤ−マンニトールから選択される少なくとも１種である、〔１〕記載の口腔内崩壊錠；
〔３〕 糖または糖アルコールが、Ｄ−マンニトールである、〔１〕記載の口腔内崩壊錠；
〔４〕 崩壊剤が、クロスポビドンおよびトウモロコシデンプンから選択される少なくとも１種である、〔１〕記載の口腔内崩壊錠；
〔５〕 崩壊剤が、クロスポビドンである、〔１〕記載の口腔内崩壊錠；
〔６〕 さらに冷水可溶分が１０重量％未満である部分アルファー化デンプンを含有する、〔１〕記載の口腔内崩壊錠；
〔７〕 冷水可溶分が１０〜２０重量％である部分アルファー化デンプンの含有量が、製剤１００重量部に対して０．５〜３０重量部である、〔１〕記載の口腔内崩壊錠；
〔８〕 （Ｉ）ａ）活性成分、ｂ）糖または糖アルコール、およびｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを含有する造粒物と、（II）崩壊剤とを含有する口腔内崩壊錠；
〔９〕 糖または糖アルコールが、乳糖およびＤ−マンニトールから選択される少なくとも１種である、〔８〕記載の口腔内崩壊錠；
〔１０〕 糖または糖アルコールが、Ｄ−マンニトールである、〔８〕記載の口腔内崩壊錠；
〔１１〕 崩壊剤が、クロスポビドンおよびトウモロコシデンプンからなる群から選択される少なくとも１種である、〔８〕記載の口腔内崩壊錠；
〔１２〕 崩壊剤が、クロスポビドンである、〔８〕記載の口腔内崩壊錠；
〔１３〕 造粒物が、さらに冷水可溶分が１０重量％未満である部分アルファー化デンプンを含有する、〔８〕記載の口腔内崩壊錠；
〔１４〕 活性成分が、ミチグリニドカルシウム水和物である、〔１〕または〔８〕項記載の口腔内崩壊錠；
〔１５〕 活性成分が、塩酸リトドリンである、〔１〕または〔８〕項記載の口腔内崩壊錠；
〔１６〕 ａ）活性成分、ｂ）糖または糖アルコール、およびｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを含有する造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法；
〔１７〕 造粒物が、さらに冷水可溶分が１０重量％未満である部分アルファー化デンプンを含有する、〔１６〕記載の製造方法；
〔１８〕 ａ）活性成分およびｂ）糖または糖アルコールを含有する混合物を、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを噴霧しながら造粒し、得られた造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法；
〔１９〕 混合物が、さらに冷水可溶分が１０重量％未満である部分アルファー化デンプンを含有する、〔１８〕記載の製造方法；
〔２０〕 ａ）活性成分、ｂ）糖または糖アルコール、およびｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、得られた造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法；および
〔２１〕 ａ）活性成分、ｂ）糖または糖アルコール、ｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプン、およびｄ）冷水可溶分が１０重量％未満である部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、得られた造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法、に関する。That is, the present invention
[1] An orally disintegrating tablet containing a) an active ingredient, b) a sugar or sugar alcohol, c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, and d) a disintegrant;
[2] The orally disintegrating tablet according to [1], wherein the sugar or sugar alcohol is at least one selected from lactose and D-mannitol;
[3] The orally disintegrating tablet according to [1], wherein the sugar or sugar alcohol is D-mannitol;
[4] The orally disintegrating tablet according to [1], wherein the disintegrant is at least one selected from crospovidone and corn starch;
[5] The orally disintegrating tablet according to [1], wherein the disintegrant is crospovidone;
[6] The orally disintegrating tablet according to [1], further comprising partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[7] The orally disintegrating tablet according to [1], wherein the content of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is 0.5 to 30 parts by weight with respect to 100 parts by weight of the preparation ;
[8] Granulated product containing (I) a) active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, and (II) a disintegrant. Orally disintegrating tablets containing:
[9] The orally disintegrating tablet according to [8], wherein the sugar or sugar alcohol is at least one selected from lactose and D-mannitol;
[10] The orally disintegrating tablet according to [8], wherein the sugar or sugar alcohol is D-mannitol;
[11] The orally disintegrating tablet according to [8], wherein the disintegrant is at least one selected from the group consisting of crospovidone and corn starch;
[12] The orally disintegrating tablet according to [8], wherein the disintegrant is crospovidone;
[13] The orally disintegrating tablet according to [8], wherein the granulated product further contains a partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[14] The orally disintegrating tablet according to [1] or [8], wherein the active ingredient is mitiglinide calcium hydrate;
[15] The orally disintegrating tablet according to [1] or [8], wherein the active ingredient is ritodrine hydrochloride;
[16] A disintegrant is mixed into a granulated product containing a) an active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, followed by compression molding. A method for producing an orally disintegrating tablet, comprising:
[17] The production method according to [16], wherein the granulated product further contains partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[18] A granulated product obtained by granulating a mixture containing a) active ingredient and b) sugar or sugar alcohol while spraying partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight. A method for producing an orally disintegrating tablet, comprising mixing a disintegrant and compression molding;
[19] The production method according to [18], wherein the mixture further contains partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[20] A mixture containing a) an active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is granulated while adding water. A method for producing an orally disintegrating tablet comprising mixing a disintegrant with the granulated product and compression molding; and [21] a) active ingredient, b) sugar or sugar alcohol, c) cold water acceptable A mixture containing partially pregelatinized starch having a soluble content of 10-20% by weight and d) partially pregelatinized starch having a cold water soluble content of less than 10% by weight is obtained by granulating with addition of water. The present invention relates to a method for producing an orally disintegrating tablet, wherein a disintegrant is mixed with a granulated product and compression molded.
本発明の口腔内崩壊錠に適用される活性成分としては、特に制限はなく、経口投与が可能であるいかなる活性成分を用いることができる。このような活性成分としては、例えば、抗パーキンソン病薬、抗高脂血症剤、抗糖尿病薬、気管支喘息治療剤、アレルギー性疾患治療剤、切迫流・早産治療薬、排尿障害治療薬などから選ばれる１種または２種以上の成分が用いられる。抗パーキンソン病薬としては、例えば、Ｌ−ドパ、カベルゴリンなどが挙げられる。抗高脂血症剤としては、例えば、ベザフィブラート、フェノフィブラート、シンフィブラートなどが挙げられる。抗糖尿病薬としては、例えば、ミチグリニドカルシウム水和物、ナテグリニドなどが挙げられる。気管支喘息治療剤としては、例えば、塩酸オザグレルなどが挙げられる。アレルギー性疾患治療剤としては、例えば、トラニラストなどが挙げられる。切迫流・早産治療薬としては、例えば、塩酸リトドリンなどが挙げられる。排尿障害治療薬としては、例えば、シロドシンなどが挙げられる。本発明の口腔内崩壊錠において、好適な活性成分は、ミチグリニドカルシウム水和物、塩酸リトドリン、シロドシンまたはカベルゴリンである。 The active ingredient applied to the orally disintegrating tablet of the present invention is not particularly limited, and any active ingredient that can be administered orally can be used. Examples of such active ingredients include antiparkinsonian drugs, antihyperlipidemic drugs, antidiabetic drugs, bronchial asthma drugs, allergic disease drugs, urgency / premature birth drugs, urination disorder drugs, etc. One or more selected components are used. Examples of the antiparkinsonian drug include L-dopa, cabergoline and the like. Examples of the antihyperlipidemic agent include bezafibrate, fenofibrate, simfibrate and the like. Examples of the antidiabetic drug include mitiglinide calcium hydrate, nateglinide and the like. Examples of the bronchial asthma therapeutic agent include ozagrel hydrochloride. Examples of the allergic disease therapeutic agent include tranilast. Examples of the treatment for urgency / premature birth include ritodrine hydrochloride and the like. Examples of the urination disorder therapeutic agent include silodosin. In the orally disintegrating tablet of the present invention, the preferred active ingredient is mitiglinide calcium hydrate, ritodrine hydrochloride, silodosin or cabergoline.
本発明の口腔内崩壊錠において、活性成分の含有量は、その種類によっても異なるが、通常、錠剤１００重量部に対して約０．０１〜約５０重量部、好ましくは約０．０１〜約２０重量部である。活性成分としてミチグリニドカルシウム水和物を用いる場合、ミチグリニドカルシウム水和物の含有量は、錠剤１００重量部に対して約１〜約２０重量部、好ましくは約１〜約１０重量部、さらに好ましくは約２〜約５重量部である。 In the orally disintegrating tablet of the present invention, the content of the active ingredient varies depending on the type, but is usually about 0.01 to about 50 parts by weight, preferably about 0.01 to about 50 parts by weight with respect to 100 parts by weight of the tablet. 20 parts by weight. When mitiglinide calcium hydrate is used as the active ingredient, the content of mitiglinide calcium hydrate is about 1 to about 20 parts by weight, preferably about 1 to about 10 parts by weight, more preferably 100 parts by weight of tablet. About 2 to about 5 parts by weight.
本発明の口腔内崩壊錠に用いられる、糖または糖アルコールとしては、水溶性が高く、成形性が低いものが好適に使用される。このような糖または糖アルコールとしては、例えば、乳糖、グルコース、蔗糖、果糖などの糖；およびＤ−マンニトール、キシリトール、マルチトール、ソルビトールなどの糖アルコールが挙げられ、乳糖またはＤ−マンニトールが、服用の際、良好な甘味を有するので好適であり、Ｄ−マンニトールが、清涼な服用感を有し、適度な硬度と速やかな崩壊性を得やすいので特に好適である。
これらの糖または糖アルコールは、必要に応じて、２種以上を組み合わせて用いることができる。また、糖と糖アルコールとを、組み合わせて用いることもできる。As the sugar or sugar alcohol used in the orally disintegrating tablet of the present invention, those having high water solubility and low moldability are preferably used. Examples of such sugars or sugar alcohols include sugars such as lactose, glucose, sucrose, and fructose; and sugar alcohols such as D-mannitol, xylitol, maltitol, and sorbitol, and lactose or D-mannitol is taken. In this case, D-mannitol is preferable because it has a good sweetness, and D-mannitol is particularly preferable because it has a refreshing feeling and can easily obtain an appropriate hardness and quick disintegration.
These sugars or sugar alcohols can be used in combination of two or more as required. In addition, sugars and sugar alcohols can be used in combination.
本発明の口腔内崩壊錠において、糖または糖アルコールの含有量は、錠剤１００重量部に対して約１０〜約９５重量部、好ましくは約３０〜約９０重量部、さらに好ましくは約５０〜約９０重量部である。 In the orally disintegrating tablet of the present invention, the sugar or sugar alcohol content is about 10 to about 95 parts by weight, preferably about 30 to about 90 parts by weight, more preferably about 50 to about 90 parts by weight per 100 parts by weight of the tablet. 90 parts by weight.
本発明の口腔内崩壊錠において、糖と糖アルコールとを組み合わせて使用する場合、糖と糖アルコールの含有量は任意の比率で用いることができるが、好ましくは、糖：糖アルコールが、０：１〜約９：約１の範囲で用いられる。 In the orally disintegrating tablet of the present invention, when sugar and sugar alcohol are used in combination, the content of sugar and sugar alcohol can be used in any ratio, but preferably sugar: sugar alcohol is 0: It is used in the range of 1 to about 9: about 1.
本発明において「冷水可溶分（重量％）」は、次のようにして測定することができる。
試料３ｇ（無水換算）を精秤し、２５℃の精製水２９７ｍＬを加え、１５００ｒｐｍで２分間高速撹拌する。得られた懸濁液を丸底遠心管に移し、２０００ｒｐｍで１５分間遠心分離する。秤量瓶に上澄み液３０ｍＬをとり、１０５℃で重量が一定になるまで乾燥する。秤量瓶中の乾燥物重量を１０００倍し、最初の試料の乾燥物重量で割った値を冷水可溶分（重量％）とする。In the present invention, “cold water soluble content (% by weight)” can be measured as follows.
3 g (anhydrous conversion) of the sample is precisely weighed, 297 mL of 25 ° C. purified water is added, and the mixture is stirred at 1500 rpm for 2 minutes at high speed. The resulting suspension is transferred to a round bottom centrifuge tube and centrifuged at 2000 rpm for 15 minutes. Take 30 mL of the supernatant in a weighing bottle and dry at 105 ° C. until the weight is constant. The dry matter weight in the weighing bottle is multiplied by 1000, and the value divided by the dry matter weight of the first sample is taken as the cold water soluble content (% by weight).
本発明において、「冷水可溶分が１０〜２０重量％である部分アルファー化デンプン」とは、上記測定法に従って冷水可溶分を測定したときに、上澄み液中に含まれる部分、すなわち、水に溶解する部分が１０〜２０重量％である部分アルファー化デンプンを意味する。また本発明において、「冷水可溶分が１０重量％未満である部分アルファー化デンプン」とは、上記測定法に従って冷水可溶分を測定したときに、水に溶解する部分が１０重量％未満の部分アルファー化デンプンを意味する。 In the present invention, “partially pregelatinized starch having a cold water-soluble content of 10 to 20% by weight” means a portion contained in a supernatant liquid, that is, water when the cold water-soluble content is measured according to the above-described measurement method. This means a partially pregelatinized starch having a portion dissolved in 10 to 20% by weight. In the present invention, “partially pregelatinized starch having a cold water-soluble content of less than 10% by weight” means that the portion dissolved in water is less than 10% by weight when the cold water-soluble content is measured according to the above-described measurement method. It means partially pregelatinized starch.
本発明の口腔内崩壊錠に用いられる部分アルファー化デンプンは、トウモロコシ、コムギ、コメなどの穀物デンプンを物理的に変性させることによって得られるものであり、その種類は特に限定されないが、トウモロコシデンプンを原料として調製された部分アルファー化デンプンが好適である。 The partially pregelatinized starch used in the orally disintegrating tablet of the present invention is obtained by physically modifying cereal starches such as corn, wheat, rice and the like, and the type thereof is not particularly limited. Partially pregelatinized starch prepared as a raw material is preferred.
本発明者ら、アルファー化の度合いや加工の異なるデンプン類について種々、検討した結果、部分アルファー化デンプンの中でも「冷水可溶分が１０〜２０重量％である部分アルファー化デンプン」を配合する場合に、予想外にも圧縮成形時における打錠障害が改善されるということを見出した。この部分アルファー化デンプンの冷水可溶分は、後述する試験例に示すように、冷水可溶分が１０重量％未満である部分アルファー化デンプンや未加工デンプンでは、打錠障害改善効果は認められず、また、アルファー化デンプンのように水に可溶性のデンプン類でも打錠障害改善効果は認められなかった。また、水に易溶性のデキストリンでは、後述するように速やかな崩壊性が得られなかった。 As a result of various studies on starches having different degrees of alphalation and processing, the present inventors have formulated "partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight" among the partially pregelatinized starches. In addition, it has been unexpectedly found that the tableting trouble at the time of compression molding is improved. The cold water soluble content of this partially pregelatinized starch, as shown in the test examples to be described later, is confirmed to have a tableting disorder improving effect with partially pregelatinized starch and raw starch whose cold water soluble content is less than 10% by weight. In addition, even in starches that are soluble in water, such as pregelatinized starch, the effect of improving tableting trouble was not observed. Also, dextrins that are readily soluble in water did not provide rapid disintegration as described later.
本発明の口腔内崩壊錠に用いられる、「冷水可溶分が１０〜２０重量％である部分アルファー化デンプン」は、市販されている部分アルファー化デンプン、例えば、Starch1500（日本カラコン製、冷水可溶分：１０〜２０重量％）を用いることができる。
また、「冷水可溶分が１０〜２０重量％である部分アルファー化デンプン」と組み合わせて使用される「冷水可溶分が１０重量％未満である部分アルファー化デンプン」としては、例えば、ＰＣＳ（旭化成工業製、冷水可溶分：１０重量％未満）、LYCATAB C（ロケット製）などを用いることができる。
また、「冷水可溶分が１０〜２０重量％である部分アルファー化デンプン」および「冷水可溶分が１０重量％未満である部分アルファー化デンプン」は、公知の方法、例えば、特公昭５９−４７６００、特開平４−３１８００１などに記載された方法に従って製造することもできる。The “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” used for the orally disintegrating tablet of the present invention is a commercially available partially pregelatinized starch such as Starch 1500 (manufactured by Nippon Colorcon, cold water is acceptable). Solute: 10 to 20% by weight) can be used.
Examples of the “partially pregelatinized starch having a cold water soluble content of less than 10% by weight” used in combination with the “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” include, for example, PCS ( Asahi Kasei Kogyo Co., Ltd., cold water soluble content: less than 10% by weight), LYCATAB C (manufactured by rocket), etc. can be used.
Further, “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” and “partially pregelatinized starch having a cold water soluble content of less than 10% by weight” are known methods, for example, JP-B-59- 47600, JP-A-4-31801 and the like.
本発明の口腔内崩壊錠に用いられる、「冷水可溶分が１０〜２０重量％である部分アルファー化デンプン」の冷水可溶分は、好ましくは約１２〜約１８重量％であり、さらに好ましくは約１４〜約１６重量％である。また、本発明の口腔内崩壊錠に用いられる、「冷水可溶分が１０重量％未満である部分アルファー化デンプン」の冷水可溶分は、好ましくは約１〜約８重量％であり、さらに好ましくは約１〜約６重量％であり、なおさらに好ましくは約１〜約３重量％である。 The cold water soluble content of the “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” used in the orally disintegrating tablet of the present invention is preferably about 12 to about 18% by weight, and more preferably Is from about 14 to about 16 weight percent. In addition, the cold water soluble content of the “partially pregelatinized starch having a cold water soluble content of less than 10% by weight” used in the orally disintegrating tablet of the present invention is preferably about 1 to about 8% by weight, Preferably from about 1 to about 6 weight percent, and even more preferably from about 1 to about 3 weight percent.
本発明の口腔内崩壊錠において、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンの含有量は、錠剤１００重量部に対し、通常、約０．５〜約３０重量部であり、錠剤１００重量部に対して０．５重量部未満であると十分な打錠障害改善効果は得られず、３０重量部を超えると速やかな崩壊性が得られない。冷水可溶分が１０〜２０重量％である部分アルファー化デンプンの好ましい含有量は、錠剤１００重量部に対して、約１〜約２０重量部であり、さらに好ましくは約２〜約１５重量部である。 In the orally disintegrating tablet of the present invention, the content of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is usually about 0.5 to about 30 parts by weight with respect to 100 parts by weight of the tablet. When the amount is less than 0.5 part by weight relative to 100 parts by weight of the tablet, a sufficient tableting trouble improving effect cannot be obtained, and when it exceeds 30 parts by weight, quick disintegration cannot be obtained. The content of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is about 1 to about 20 parts by weight, more preferably about 2 to about 15 parts by weight, based on 100 parts by weight of the tablet. It is.
また、本発明の口腔内崩壊錠において、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンと、冷水可溶分が１０重量％未満である部分アルファー化デンプンとを組み合わせて使用する場合、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンと、冷水可溶分が１０重量％未満である部分アルファー化デンプンとの比率は、１：０〜約１：約９、好ましくは約２：約１〜約１：約９の範囲で用いられる。 In the orally disintegrating tablet of the present invention, a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight and a partially pregelatinized starch having a cold water soluble content of less than 10% by weight are used in combination. The ratio of partially pregelatinized starch having a cold water soluble content of 10-20% by weight to partially pregelatinized starch having a cold water soluble content of less than 10% by weight is 1: 0 to about 1: about 9, Preferably it is used in the range of about 2: about 1 to about 1: about 9.
本発明の口腔内崩壊錠に用いられる崩壊剤としては、例えば、クロスポビドン、トウモロコシデンプンなどが挙げられ、好適にはクロスポビドンである。 Examples of the disintegrant used in the orally disintegrating tablet of the present invention include crospovidone and corn starch, and crospovidone is preferred.
本発明の口腔内崩壊錠において、崩壊剤の含有量は、崩壊錠の種類によっても異なるが、錠剤１００重量部に対し、通常、約０．５〜約３０重量部である。より具体的には、クロスポビドンの含有量は、錠剤１００重量部に対して約０．５〜約１０重量部であり、好ましくは約１〜約７重量部である。トウモロコシデンプンの含有量は、錠剤１００重量部に対して約３〜約２０重量部であり、好ましくは約５〜約２０重量部である。 In the orally disintegrating tablet of the present invention, the content of the disintegrant varies depending on the type of disintegrating tablet, but is usually about 0.5 to about 30 parts by weight with respect to 100 parts by weight of the tablet. More specifically, the content of crospovidone is about 0.5 to about 10 parts by weight, preferably about 1 to about 7 parts by weight, based on 100 parts by weight of the tablet. The content of corn starch is about 3 to about 20 parts by weight, preferably about 5 to about 20 parts by weight, based on 100 parts by weight of the tablet.
また、本発明の口腔内崩壊錠は、発明の効果に支障のない限り、製剤の製造に用いられる種々の添加剤、例えば、賦形剤、結合剤、滑沢剤、甘味料、酸味料、発泡剤、香料、着色剤などを適量含有することができる。 In addition, the orally disintegrating tablet of the present invention has various additives used in the preparation of the preparation, for example, excipients, binders, lubricants, sweeteners, acidulants, as long as the effects of the invention are not hindered. An appropriate amount of a foaming agent, a fragrance, a colorant, and the like can be contained.
このような賦形剤としては、例えば、コメデンプン、結晶セルロース、無水リン酸カルシウム、沈降炭酸カルシウム、ケイ酸カルシウム、乳酸カルシウム、エチルセルロースなどが挙げられる。結合剤としては、例えば、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドン、メチルセルロース、ポリビニルアルコール、アルギン酸ナトリウム、アミノアルキルメタクリレートコポリマー、ポリエチレングリコールなどが挙げられる。滑沢剤としては、例えば、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、軽質無水ケイ酸、蔗糖脂肪酸エステル、フマル酸ステアリルナトリウムなどが挙げられる。甘味料としては、例えば、アスパルテーム（登録商標）、サッカリンナトリウム、グリチルリチン二カリウム、ステビア、ソーマチン、アセサルファムＫなどが挙げられる。酸味料としては、例えば、クエン酸、酒石酸、リンゴ酸、アスコルビン酸などが挙げられる。発泡剤としては、例えば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カルシウムなどが挙げられる。矯味剤としては、例えば、L-アスパラギン酸、塩化ナトリウム、塩化マグネシウム、クエン酸ナトリウム、クエン酸カルシウム、L-グルタミン酸ナトリウム、炭酸水素ナトリウムなどが挙げられる。香料としては、例えば、オレンジ油、レモン油、メントール、および各種香料粉末などが挙げられる。着色剤としては、例えば、食用黄色５号、食用赤色２号、食用青色２号などの食用色素、黄色三二酸化鉄、三二酸化鉄、カラメル色素などが挙げられる。 Examples of such excipients include rice starch, crystalline cellulose, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, calcium lactate, and ethyl cellulose. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, methylcellulose, polyvinyl alcohol, sodium alginate, aminoalkyl methacrylate copolymer, polyethylene glycol and the like. Examples of the lubricant include magnesium stearate, calcium stearate, talc, light anhydrous silicic acid, sucrose fatty acid ester, sodium stearyl fumarate and the like. Examples of the sweetener include aspartame (registered trademark), saccharin sodium, dipotassium glycyrrhizin, stevia, thaumatin, and acesulfame K. Examples of the sour agent include citric acid, tartaric acid, malic acid, ascorbic acid and the like. Examples of the foaming agent include sodium hydrogen carbonate, sodium carbonate, calcium carbonate and the like. Examples of the corrigent include L-aspartic acid, sodium chloride, magnesium chloride, sodium citrate, calcium citrate, sodium L-glutamate, sodium bicarbonate and the like. Examples of the fragrances include orange oil, lemon oil, menthol, and various fragrance powders. Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 2, and edible blue No. 2, yellow ferric oxide, ferric oxide, and caramel pigment.
次に本発明の口腔内崩壊錠の製造方法について説明する。 Next, the manufacturing method of the orally disintegrating tablet of this invention is demonstrated.
本発明の口腔内崩壊錠は、ａ）活性成分、ｂ）糖または糖アルコール、およびｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを含有する造粒物に、崩壊剤を添加、混合し、圧縮成形することにより、製造することができる。このように本発明の口腔内崩壊錠の製造方法では、造粒物中に冷水可溶分が１０〜２０重量％である部分アルファー化デンプンが含まれるのが特徴であり、造粒物中に糖または糖アルコールとともに冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを共存させることにより、圧縮成形時の打錠障害を改善することができる。 The orally disintegrating tablet of the present invention comprises a granulated material containing a) an active ingredient, b) a sugar or sugar alcohol, and c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight. Can be produced by adding, mixing, and compression molding. Thus, in the method for producing an orally disintegrating tablet of the present invention, the granulated product is characterized in that partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is contained in the granulated product. By coexisting sugar or sugar alcohol with partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, it is possible to improve tableting troubles during compression molding.
また、本発明の口腔内崩壊錠において、造粒物中の活性成分は任意の量を含有させることが可能であり、発明の効果に支障のない限り、糖または糖アルコールおよび部分アルファー化デンプンからなる造粒物に、活性成分および崩壊剤を添加、混合し、圧縮成形して製造することも可能である。 Moreover, in the orally disintegrating tablet of the present invention, the active ingredient in the granulated product can be contained in any amount, and from sugar or sugar alcohol and partially pregelatinized starch as long as the effect of the invention is not hindered. It is also possible to add an active ingredient and a disintegrant to the resulting granulated product, mix, and compression-mold.
また、上記造粒物中に、さらに冷水可溶分が１０重量％未満である部分アルファー化デンプンを添加することによって崩壊性を増強することができ、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンと、冷水可溶分が１０重量％未満である部分アルファー化デンプンの添加量を適宜増減することにより、口腔内における崩壊時間を好ましい時間に調節することができる。 Moreover, disintegration can be enhanced by adding a partially pregelatinized starch having a cold water soluble content of less than 10% by weight to the granulated product, and the cold water soluble content is 10 to 20% by weight. The disintegration time in the oral cavity can be adjusted to a preferred time by appropriately increasing or decreasing the addition amount of a certain partially pregelatinized starch and a partially pregelatinized starch having a cold water soluble content of less than 10% by weight.
本発明の口腔内崩壊錠に用いられる造粒方法としては、例えば、流動層造粒法、高速撹拌造粒法、押し出し造粒法、転動造粒法、転動流動造粒法などが挙げられ、好適には流動層造粒法、高速撹拌造粒法が用いられる。 Examples of the granulation method used for the orally disintegrating tablet of the present invention include a fluidized bed granulation method, a high speed stirring granulation method, an extrusion granulation method, a rolling granulation method, and a rolling fluid granulation method. Preferably, a fluidized bed granulation method or a high speed stirring granulation method is used.
本発明の口腔内崩壊錠は、例えば、以下のようにして製造することができる。 The orally disintegrating tablet of the present invention can be produced, for example, as follows.
製法１
本発明の口腔内崩壊錠は、ａ）活性成分およびｂ）糖または糖アルコールを含有する混合物を、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを噴霧しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。また、上記の造粒工程において、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンの一部を、活性成分および糖または糖アルコールと混合し、残りの部分アルファー化デンプンを噴霧しながら造粒することもできる。Manufacturing method 1
The orally disintegrating tablet of the present invention is a granulated mixture containing a) active ingredient and b) sugar or sugar alcohol while spraying partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, It can manufacture by adding a disintegrating agent to the said granulated material, mixing, and compression-molding. In the granulation step, a part of the partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is mixed with the active ingredient and sugar or sugar alcohol, and the remaining partially pregelatinized starch is sprayed. It can also be granulated.
製法２
また、本発明の口腔内崩壊錠は、ａ）活性成分、ｂ）糖または糖アルコール、およびｃ）冷水可溶分が１０重量％未満である部分アルファー化デンプンを含有する混合物を、冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを噴霧しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。Manufacturing method 2
In addition, the orally disintegrating tablet of the present invention comprises a mixture containing a) active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of less than 10% by weight, which is soluble in cold water. It can be produced by granulating a partially pregelatinized starch having a content of 10 to 20% by weight while spraying, adding a disintegrant to the granulated product, mixing, and compression molding.
製法３
また、本発明の口腔内崩壊錠は、ａ）活性成分、ｂ）糖または糖アルコール、およびｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。Manufacturing method 3
Moreover, the orally disintegrating tablet of the present invention comprises a mixture containing a) an active ingredient, b) a sugar or sugar alcohol, and c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight. It can be manufactured by granulating while adding, adding a disintegrant to the granulated product, mixing, and compression molding.
製法４
また、本発明の口腔内崩壊錠は、ａ）活性成分、ｂ）糖または糖アルコール、ｃ）冷水可溶分が１０〜２０重量％である部分アルファー化デンプン、およびｄ）１０重量％未満の冷水可溶分を有する部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。Manufacturing method 4
Also, the orally disintegrating tablet of the present invention comprises: a) an active ingredient, b) a sugar or sugar alcohol, c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, and d) less than 10% by weight A mixture containing partially pregelatinized starch having a cold water soluble content can be produced by granulating while adding water, adding a disintegrant to the granulated product, mixing, and compression molding.
上記の製法１〜４において、糖と糖アルコールとを組み合わせて使用する場合、糖および糖アルコールの双方を活性成分と混合、造粒してもよいが、いずれか一方を造粒物中に含有させ、他方を造粒後に添加、混合してもよい。好ましくは、活性成分と糖アルコールとを含有する混合物を造粒し、得られた造粒物に、糖および崩壊剤を添加、混合することにより、圧縮成形時の打錠障害を生じることなく、本発明の口腔内崩壊錠を調製することができる。 In the above production methods 1 to 4, when sugar and sugar alcohol are used in combination, both the sugar and sugar alcohol may be mixed with the active ingredient and granulated, but either one is contained in the granulated product. The other may be added and mixed after granulation. Preferably, a mixture containing an active ingredient and a sugar alcohol is granulated, and a sugar and a disintegrant are added to and mixed with the obtained granulated product, without causing a tableting trouble during compression molding. The orally disintegrating tablet of the present invention can be prepared.
また、上記の製法１〜４において、造粒後、必要に応じて、滑沢剤、甘味料、発泡剤、酸味料、矯味剤、香料などを適量、混合してもよい。 Moreover, in said manufacturing methods 1-4, after granulation, you may mix a lubricant, a sweetener, a foaming agent, a sour agent, a corrigent, a fragrance | flavor, etc. in a proper quantity as needed.
本発明の口腔内崩壊錠において、圧縮成形は、単発打錠機、ロータリー打錠機などを用いて行うことができる。打錠する際の圧力は、通常、２〜６０ｋＮ／ｃｍ２であり、好適には６〜３０ｋＮ／ｃｍ２である。In the orally disintegrating tablet of the present invention, compression molding can be performed using a single tableting machine, a rotary tableting machine or the like. The pressure at the time of tableting is usually 2 to 60 kN / cm 2 , and preferably 6 to 30 kN / cm 2 .
このようにして得られる本発明の口腔内崩壊錠は、適度な硬度と、口腔内での速やかな崩壊性または溶解性を示す。本発明の口腔内崩壊錠の口腔内崩壊時間は、錠剤の大きさや厚みによっても異なるが、通常、６０秒以内であり、好適には４０秒以内である。また、本発明の口腔内崩壊錠の硬度は、通常、３０Ｎ以上であり、好適には５０Ｎ以上である。 The orally disintegrating tablet of the present invention thus obtained exhibits moderate hardness and rapid disintegration or solubility in the oral cavity. The oral disintegration time of the orally disintegrating tablet of the present invention varies depending on the size and thickness of the tablet, but is usually within 60 seconds, and preferably within 40 seconds. Moreover, the hardness of the orally disintegrating tablet of the present invention is usually 30 N or more, and preferably 50 N or more.
本発明の口腔内崩壊錠は、口腔内において速やかに崩壊もしくは溶解するので、高齢者、小児や嚥下困難な患者が服用しやすい。また、本発明の口腔内崩壊錠は、流通過程で損傷しない十分な硬度を有するので取り扱いが容易である。さらに、本発明の口腔内崩壊錠は、製造過程において打錠障害等の問題を生じることなく容易に製造することができるので、工業的生産に適している。 Since the orally disintegrating tablet of the present invention rapidly disintegrates or dissolves in the oral cavity, it is easy for the elderly, children, and patients who have difficulty swallowing. In addition, the orally disintegrating tablet of the present invention is easy to handle because it has sufficient hardness so as not to be damaged in the distribution process. Furthermore, since the orally disintegrating tablet of the present invention can be easily produced without causing problems such as tableting troubles in the production process, it is suitable for industrial production.
本発明の内容を以下の実施例、比較例および試験例によりさらに詳細に説明するが、本発明の内容はこれらに限定されるものではない。 The content of the present invention will be described in more detail with reference to the following examples, comparative examples and test examples, but the content of the present invention is not limited to these.
試験例１
冷水可溶分の測定
デンプン類として、トウモロコシデンプン、部分アルファー化デンプンおよびアルファー化デンプン、並びにデキストリンの冷水可溶分を、以下の方法に従って測定した。Test example 1
Measurement of cold water soluble content As starches, corn starch, partially pregelatinized starch and pregelatinized starch, and cold water soluble content of dextrin were measured according to the following method.
試料３ｇ（無水換算）を精秤し、２５℃の精製水２９７ｍＬを加え、１５００ｒｐｍで２分間高速撹拌した。得られた懸濁液を丸底遠心管に移し、２０００ｒｐｍで１５分間遠心分離した。秤量瓶に上澄み液３０ｍＬをとり、１０５℃で重量が一定になるまで乾燥した。秤量瓶中の乾燥物重量を１０００倍し、最初の試料の乾燥物重量で割った値を冷水可溶分（重量％）とした。結果を表１に示した。 3 g (anhydrous conversion) of the sample was precisely weighed, 297 mL of purified water at 25 ° C. was added, and the mixture was stirred at 1500 rpm for 2 minutes at high speed. The resulting suspension was transferred to a round bottom centrifuge tube and centrifuged at 2000 rpm for 15 minutes. 30 mL of the supernatant was placed in a weighing bottle and dried at 105 ° C. until the weight was constant. The value obtained by multiplying the dry matter weight in the weighing bottle by 1000 and dividing by the dry matter weight of the first sample was taken as the cold water soluble content (% by weight). The results are shown in Table 1.
試験例２
硬度試験
実施例１〜１１および比較例１〜８で製造した錠剤の硬度を、硬度計（TS-75N，岡田精工製）を用いて測定した。なお、試験は３錠で行い、平均値を求めた。結果を表２および表３に示した。Test example 2
Hardness Test The hardness of the tablets produced in Examples 1 to 11 and Comparative Examples 1 to 8 was measured using a hardness meter (TS-75N, manufactured by Okada Seiko). The test was performed with 3 tablets, and the average value was obtained. The results are shown in Tables 2 and 3.
試験例３
口腔内崩壊試験
健常人男性３名において、実施例１〜１１および比較例１〜８で製造した錠剤１錠を口腔内に含み、舌で軽く転がしながら錠剤が崩壊した時間を測定し、その平均値を求めた。結果を表２および表３に示した。Test example 3
Oral disintegration test In 3 healthy males, one tablet produced in Examples 1 to 11 and Comparative Examples 1 to 8 was included in the oral cavity, and the time when the tablet disintegrated was measured while gently rolling with the tongue. The value was determined. The results are shown in Tables 2 and 3.
試験例４
打錠障害性
実施例１〜１１および比較例１〜８の打錠工程において、錠剤の上下表面の外観からスティッキングの有無、錠剤側面の外観からバインディングの有無、錠剤の層状剥離の発生からキャッピングの有無を観察した。また、臼壁への粉の付着あるいは摩擦状況（異音の発生）がひどい場合は、打錠不可とした。結果を表２および表３に示した。Test example 4
Tabletting obstacle In the tableting process of Examples 1 to 11 and Comparative Examples 1 to 8, capping from the appearance of the upper and lower surfaces of the tablet, the presence or absence of sticking from the appearance of the side of the tablet, the occurrence of delamination of the tablet The presence or absence was observed. In addition, when powder adheres to the mortar wall or the frictional state (occurrence of abnormal noise) is severe, tableting is not possible. The results are shown in Tables 2 and 3.
実施例１
Ｄ−マンニトール 181.0 mg
部分アルファー化デンプン（Starch1500） 6.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間解砕したＤ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）633.5gを流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧7.8、11.7および15.6kN/cm２の条件で錠剤を製した。Example 1
D-mannitol 181.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
Fluidized bed granulation drying of 633.5g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45μm) pulverized for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek) Into the machine (LAB-1, Paulek), and 21 g of partially pregelatinized starch (Starch 1500, Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. Granulation was performed while spraying. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 7.8, 11.7 and 15.6 kN / cm 2 Tablets were made.
実施例２
Ｄ−マンニトール 177.0 mg
部分アルファー化デンプン（Starch1500） 10.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）619.5gと部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）14gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧7.8、11.7および15.6kN/cm２の条件で錠剤を製した。Example 2
D-mannitol 177.0 mg
Partially pregelatinized starch (Starch1500) 10.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 619.5g and partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) 14g Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 7.8, 11.7 and 15.6 kN / cm 2 Tablets were made.
実施例３
Ｄ−マンニトール 161.0 mg
部分アルファー化デンプン（Starch1500） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gと部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）70gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7、15.6および19.5kN/cm２の条件で錠剤を製した。Example 3
D-mannitol 161.0 mg
Partially pregelatinized starch (Starch1500) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon Co., Ltd., cold water soluble content: 15.8% by weight) 70 g with high-speed mixing and granulation Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7, 15.6 and 19.5 kN / cm 2 Tablets were made.
実施例４
Ｄ−マンニトール 147.0 mg
部分アルファー化デンプン（Starch1500） 40.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）514.5gと部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）119gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm２の条件で錠剤を製した。 Example 4
D-mannitol 147.0 mg
Partially pregelatinized starch (Starch1500) 40.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 514.5 g and partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) 119 g are mixed at high speed with stirring. Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.
実施例５
Ｄ−マンニトール 152.0 mg
部分アルファー化デンプン（Starch1500） 5.0 mg
トウモロコシデンプン 40.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間解砕したＤ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）633.5gを流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物219.8g、トウモロコシデンプン（日本食品化工製）56g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）1.4gおよびステアリン酸マグネシウム（太平化学産業製）2.8gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧7.8、11.7および15.6kN/cm２の条件で錠剤を製した。Example 5
D-mannitol 152.0 mg
Partially pregelatinized starch (Starch1500) 5.0 mg
Corn starch 40.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
Fluidized bed granulation drying of 633.5g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45μm) pulverized for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek) Into the machine (LAB-1, Paulek), and 21 g of partially pregelatinized starch (Starch 1500, Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. Granulation was performed while spraying. 219.8g of granulated material sieved by No. 18 sieve, 56g of corn starch (manufactured by Nippon Shokuhin Kako), 1.4g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Industries) and 2.8g of magnesium stearate (manufactured by Taihei Chemical Industries) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 7.8, 11.7 and 15.6 kN / cm 2 Tablets were made.
実施例６
Ｄ−マンニトール 161.0 mg
部分アルファー化デンプン（Starch1500） 6.0 mg
部分アルファー化デンプン（PCS） 20.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gと部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）70gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，冷水可溶分：15.8重量％，日本カラコン製）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g，軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm２の条件で錠剤を製した。Example 6
D-mannitol 161.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Partially pregelatinized starch (PCS) 20.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) 70 g with high-speed mixing and granulation Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (Starch 1500, soluble in cold water: 15.8% by weight, manufactured by Nippon Colorcon) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved by No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.
比較例１
Ｄ−マンニトール 161.0 mg
部分アルファー化デンプン（PCS） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gと部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）70gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。Comparative Example 1
D-mannitol 161.0 mg
Partially pregelatinized starch (PCS) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) 70 g with high-speed mixing and granulation Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.
比較例２
Ｄ−マンニトール 161.0 mg
部分アルファー化デンプン（LYCATAB C） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gと部分アルファー化デンプン（LYCATAB C，ロケット製，冷水可溶分：5.1重量％）70gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（LYCATAB C，ロケット製，冷水可溶分：5.1重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。Comparative Example 2
D-mannitol 161.0 mg
Partially pregelatinized starch (LYCATAB C) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5g and partially pregelatinized starch (LYCATAB C, manufactured by Rocket, cold water soluble content: 5.1 wt%) 70g Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (LYCATAB C, manufactured by Rocket, soluble in cold water: 5.1% by weight) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.
比較例３
Ｄ−マンニトール 187.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）654.5gを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間解砕した。この解砕物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、精製水をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。Comparative Example 3
D-mannitol 187.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
654.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) was pulverized for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This pulverized product was put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and granulated while spraying purified water with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). This tableting mixture is tableted using a rotary tableting machine (Correct 12HUK, Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Made.
比較例４
Ｄ−マンニトール 161.0 mg
トウモロコシデンプン 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gとトウモロコシデンプン（日本食品化工製，冷水可溶分：0.1重量％）91gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて２分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、精製水をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7kN/cm2の条件で錠剤を製した。Comparative Example 4
D-mannitol 161.0 mg
Corn starch 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and corn starch (manufactured by Nippon Shokuhin Kako Co., Ltd., cold water soluble content: 0.1 wt%) 91 g are mixed at high speed with agitation granulator (FM -VG-10, manufactured by Paulek) and mixed for 2 minutes. This mixture was put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and granulated while spraying purified water with a spray nozzle. 374g of granulated material sieved by No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, manufactured by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Corporation) and 4g of magnesium stearate (Taipei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, tablets were produced using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 kN / cm 2 . .
比較例５
Ｄ−マンニトール 161.0 mg
アルファー化デンプン（UNI-PURE） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gとアルファー化デンプン（UNI-PURE，National Starch&Chemical製）70gを高速混合撹拌造粒機（FM-VG-10，パウレック製）とを用いて２分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別にアルファー化デンプン（UNI-PURE，National Starch&Chemical製）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm2の条件で錠剤を製した。Comparative Example 5
D-mannitol 161.0 mg
Alpha-modified starch (UNI-PURE) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and pregelatinized starch (UNI-PURE, manufactured by National Starch & Chemical) 70 g are mixed at high speed with agitation granulator (FM-VG-10, manufactured by POWREC) ) For 2 minutes. This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of pregelatinized starch (UNI-PURE, manufactured by National Starch & Chemical) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. Granulation was performed while spraying. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.
比較例６
Ｄ−マンニトール 161.0 mg
アルファー化デンプン（アミコールC） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gとアルファー化デンプン（アミコールC，日澱化学製）80gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて２分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別にアルファー化デンプン（アミコールC，日澱化学）11gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，IS製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。
Comparative Example 6
D-mannitol 161.0 mg
Alphalated starch (Amicol C) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and pregelatinized starch (Amicol C, manufactured by Nissho Chemical Co., Ltd.) 80 g were mixed at high speed with agitation granulator (FM-VG-10, For 2 minutes. This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC). Separately, 11 g of pregelatinized starch (Amicol C, Nissho Chemical) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. While granulating. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, manufactured by IS), 2g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Corporation) and 4g of magnesium stearate (produced by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.
比較例７
Ｄ−マンニトール 161.0 mg
デキストリン 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）563.5gとデキストリン（アミコール10，日澱化学製，冷水可溶分：100.0重量％）71gとを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて２分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別にデキストリン（アミコール10，日澱化学製，冷水可溶分：96.1％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm2の条件で錠剤を製した。Comparative Example 7
D-mannitol 161.0 mg
Dextrin 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and dextrin (Amicol 10, manufactured by Nissho Chemical Co., Ltd., cold water soluble content: 100.0% by weight) 71 g are mixed at high speed with agitation. (FM-VG-10, manufactured by Paulek) was mixed for 2 minutes. This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC). Separately, 21 g of dextrin (Amicol 10, manufactured by Nissho Chemical Co., Ltd., cold water soluble component: 96.1%) is dispersed in 180 g of purified water. Granulation was performed while spraying the dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.
実施例８
塩酸リトドリン 5.0 mg
Ｄ−マンニトール 156.0 mg
部分アルファー化デンプン（Starch1500） 6.0 mg
部分アルファー化デンプン（PCS） 20.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
（合計200.0 mg/１錠）
塩酸リトドリン17.5g、Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）546gおよび部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）70gを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて２分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）4gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7、15.6および19.5kN/cm2の条件で錠剤を製した。Example 8
Ritodrine hydrochloride 5.0 mg
D-mannitol 156.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Partially pregelatinized starch (PCS) 20.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)
High-speed mixing of 17.5 g of ritodrine hydrochloride, 546 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) The mixture was mixed for 2 minutes using a stirring granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7, 15.6 and 19.5 kN / cm 2 . Tablets were made.
実施例９
ミチグリニドカルシウム水和物 5.0 mg
Ｄ−マンニトール 155.0 mg
部分アルファー化デンプン（Starch1500） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
（合計200.0 mg/１錠）
ミチグリニドカルシウム水和物17.5g、Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）542.5gおよび部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）70gを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物372g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）6gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7、15.6および19.5kN/cm2の条件で錠剤を製した。Example 9
Mitiglinide calcium hydrate 5.0 mg
D-mannitol 155.0 mg
Partially pregelatinized starch (Starch1500) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)
17.5 g of mitiglinide calcium hydrate, 542.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) Was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 372g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 6g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7, 15.6 and 19.5 kN / cm 2 . Tablets were made.
実施例１０
ミチグリニドカルシウム水和物 5.0 mg
Ｄ−マンニトール 155.0 mg
部分アルファー化デンプン（Starch1500） 6.0 mg
部分アルファー化デンプン（PCS） 20.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
（合計200.0 mg/１錠）
ミチグリニドカルシウム水和物17.5g、Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）542.5gおよび部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）70gを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物372g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）6gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm2の条件で錠剤を製した。Example 10
Mitiglinide calcium hydrate 5.0 mg
D-mannitol 155.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Partially pregelatinized starch (PCS) 20.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)
17.5 g of mitiglinide calcium hydrate, 542.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) Was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 372g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 6g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.
実施例１１
ミチグリニドカルシウム水和物 10.0 mg
Ｄ−マンニトール 50.0 mg
乳糖 114.2 mg
部分アルファー化デンプン（Starch1500） 3.75 mg
部分アルファー化デンプン（PCS） 11.25 mg
クロスポビドン 6.0 mg
アスパルテーム 0.8 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
（合計200.0 mg/１錠）
ミチグリニドカルシウム水和物200g、Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）1000g、部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）225gおよび部分アルファー化デンプン（Starch1500，日本カラコン製，冷水可溶分：15.8重量％）75gを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて3分間混合した。このまま高速混合撹拌造粒機（FM-VG-10，パウレック製）中で、混合物に精製水465gを添加し造粒を行った後、湿潤した造粒物を流動層造粒乾燥機（LAB-1，パウレック）に投入し、入口温度80℃の条件で乾燥した。乾燥した造粒物を、パワーミル（P-02S、ダルトン製）を用いて整粒した。整粒した造粒物150g、乳糖（Tablettose80、メグレ製, 平均粒子径145μｍ）228.4g、クロスポビドン（Polyplasdone XL-10，ISP製）12gおよびアスパルテーム1.6gを、Ｖ型混合機（DV-1，ダルトン製）を用いて3分間混合した。さらに、ここへ軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gとステアリン酸マグネシウム（太平化学産業製）6gとを投入し、2分間混合した。この打錠用混合物をロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧19.5kN/cm2の条件で錠剤を製した。Example 11
Mitiglinide calcium hydrate 10.0 mg
D-mannitol 50.0 mg
Lactose 114.2 mg
Partially pregelatinized starch (Starch1500) 3.75 mg
Partially pregelatinized starch (PCS) 11.25 mg
Crospovidone 6.0 mg
Aspartame 0.8 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)
200 g of mitiglinide calcium hydrate, 1000 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm), 225 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) and parts Alpha starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) 75 g was mixed for 3 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). In this state, after adding 465 g of purified water to the mixture and granulating in a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek), the wet granulated product is mixed with a fluidized bed granulator / dryer (LAB-). 1), and dried at an inlet temperature of 80 ° C. The dried granulated product was sized using a power mill (P-02S, manufactured by Dalton). The granulated product 150g, lactose (Tablettose80, made by Megre, average particle size 145μm) 228.4g, crospovidone (Polyplasdone XL-10, made by ISP) 12g and aspartame 1.6g are mixed into a V-type mixer (DV-1, For 3 minutes. Further, 2 g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Corporation) and 6 g of magnesium stearate (produced by Taihei Chemical Industry) were added and mixed for 2 minutes. Tablets were produced from this tableting mixture using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho Co., Ltd.) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 19.5 kN / cm 2 .
比較例８
ミチグリニドカルシウム水和物 5.0 mg
Ｄ−マンニトール 155.0 mg
部分アルファー化デンプン（PCS） 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
（合計200.0 mg/１錠）
ミチグリニドカルシウム水和物17.5g、Ｄ−マンニトール（マンニットP，東和化成工業製, 平均粒子径45μｍ）542.5gおよび部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）70gを、高速混合撹拌造粒機（FM-VG-10，パウレック製）を用いて2分間混合した。この混合物を流動層造粒乾燥機（LAB-1，パウレック製）に投入し、別に部分アルファー化デンプン（PCS，旭化成工業製，冷水可溶分：1.2重量％）21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物372g、クロスポビドン（Polyplasdone XL-10，ISP製）20g、軽質無水ケイ酸（Adsolidar 101，フロイント産業製）2gおよびステアリン酸マグネシウム（太平化学産業製）6gを、Ｖ型混合機（DV-1，ダルトン製）を用いて２分間混合した。この打錠用混合物を、ロータリー打錠機（Correct 12HUK，菊水製作所製）を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7kN/cm2の条件で錠剤を製した。Comparative Example 8
Mitiglinide calcium hydrate 5.0 mg
D-mannitol 155.0 mg
Partially pregelatinized starch (PCS) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)
17.5 g of mitiglinide calcium hydrate, 542.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) Was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 372g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 6g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, tablets were produced using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 kN / cm 2 . .
本発明の口腔内崩壊錠は、流通過程で損傷しない十分な硬度を有し、かつ口腔内で速やかに崩壊もしくは溶解するので、高齢者、小児や嚥下困難な患者が服用しやすい剤形として有用である。 The orally disintegrating tablet of the present invention has sufficient hardness not to be damaged in the distribution process, and rapidly disintegrates or dissolves in the oral cavity, so it is useful as a dosage form that is easy to be taken by elderly people, children, and patients who have difficulty swallowing. It is.
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007502589A JP5004236B2 (en) | 2005-02-09 | 2006-02-06 | Orally disintegrating tablets |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005032978 | 2005-02-09 | ||
| JP2005032978 | 2005-02-09 | ||
| JP2007502589A JP5004236B2 (en) | 2005-02-09 | 2006-02-06 | Orally disintegrating tablets |
| PCT/JP2006/301951 WO2006085497A1 (en) | 2005-02-09 | 2006-02-06 | Tablet disintegrating in the oral cavity |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012037354A Division JP5342028B2 (en) | 2005-02-09 | 2012-02-23 | Orally disintegrating tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPWO2006085497A1 JPWO2006085497A1 (en) | 2008-06-26 |
| JP5004236B2 true JP5004236B2 (en) | 2012-08-22 |
Family
ID=36793069
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007502589A Expired - Fee Related JP5004236B2 (en) | 2005-02-09 | 2006-02-06 | Orally disintegrating tablets |
| JP2012037354A Expired - Fee Related JP5342028B2 (en) | 2005-02-09 | 2012-02-23 | Orally disintegrating tablets |
| JP2013182805A Pending JP2014001233A (en) | 2005-02-09 | 2013-09-04 | Tablet disintegrating in the oral cavity |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012037354A Expired - Fee Related JP5342028B2 (en) | 2005-02-09 | 2012-02-23 | Orally disintegrating tablets |
| JP2013182805A Pending JP2014001233A (en) | 2005-02-09 | 2013-09-04 | Tablet disintegrating in the oral cavity |
Country Status (2)
| Country | Link |
|---|---|
| JP (3) | JP5004236B2 (en) |
| WO (1) | WO2006085497A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101516403B (en) * | 2006-09-14 | 2013-10-02 | 安斯泰来制药株式会社 | Orally disintegrating tablet and process for production thereof |
| FR2933299B1 (en) * | 2008-07-04 | 2012-02-03 | Roquette Freres | MANNITOL ORODISPERSIBLE |
| NZ611467A (en) * | 2010-12-02 | 2015-06-26 | Aptalis Pharmatech Inc | Rapidly dispersing granules, orally disintegrating tablets and methods |
| WO2016051782A1 (en) * | 2014-09-30 | 2016-04-07 | キッセイ薬品工業株式会社 | Oral preparation in which bitter taste of bitter-tasting drug is masked |
| JP6128160B2 (en) * | 2015-05-07 | 2017-05-17 | ニプロ株式会社 | Method for producing orally disintegrating tablets |
| SI3701944T1 (en) * | 2015-06-18 | 2022-04-29 | Estetra Srl | Orodispersible dosage unit containing an estetrol component |
| JP6800596B2 (en) * | 2016-03-29 | 2020-12-16 | 小林製薬株式会社 | tablet |
| JP7001332B2 (en) * | 2016-03-29 | 2022-01-19 | 小林製薬株式会社 | Granulation |
| JP2019031491A (en) * | 2017-08-08 | 2019-02-28 | 日本ケミファ株式会社 | Diabetes therapeutic agent |
| WO2021095092A1 (en) * | 2019-11-11 | 2021-05-20 | 大塚製薬株式会社 | Orally disintegrating tablet |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000047233A1 (en) * | 1999-02-15 | 2000-08-17 | Sumitomo Pharmaceuticals Co., Ltd. | Tablets quickly disintegrated in the oral cavity |
| JP2000273039A (en) * | 1999-01-20 | 2000-10-03 | Taisho Pharmaceut Co Ltd | Composition disintegrable in oral cavity |
| JP2001513545A (en) * | 1997-08-22 | 2001-09-04 | スミスクライン・ビーチャム・コーポレイション | Rapidly disintegrating methylcellulose tablets |
| JP2002524410A (en) * | 1998-09-08 | 2002-08-06 | スミスクライン・ビーチャム・コーポレイション | Lipstatin derivative-soluble fiber tablet |
| JP2003055197A (en) * | 2001-06-07 | 2003-02-26 | Tanabe Seiyaku Co Ltd | Functional particle-containing intraoral disintegrative preparation |
| WO2003074029A1 (en) * | 2002-03-07 | 2003-09-12 | Vectura Limited | Fast melt multiparticulate formulations for oral delivery |
| JP2004002326A (en) * | 2002-03-22 | 2004-01-08 | Takeda Chem Ind Ltd | Rapidly disintegrating solid preparation |
| WO2004064810A1 (en) * | 2003-01-21 | 2004-08-05 | Nippon Shinyaku Co., Ltd. | Tablet quickly melting in oral cavity |
| JP2004315483A (en) * | 2003-02-28 | 2004-11-11 | Towa Yakuhin Kk | Orally disintegrating tablet |
| JP2008521808A (en) * | 2004-11-24 | 2008-06-26 | テバ ファーマシューティカル インダストリーズ リミティド | Rasagiline oral disintegrating composition |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4600579A (en) * | 1983-06-07 | 1986-07-15 | Mallinckrodt, Inc. | N-acetyl-p-aminophenol compositions containing partially gelatinized starch and method for preparing same |
| US5047246A (en) * | 1988-09-09 | 1991-09-10 | Bristol-Myers Company | Direct compression cyclophosphamide tablet |
| JPH06509073A (en) * | 1991-06-26 | 1994-10-13 | セプラコア，インコーポレーテッド | Methods and compositions for the treatment of emesis, nausea and other disorders using optically pure S(-)ondansetron |
| JPH06508836A (en) * | 1991-06-26 | 1994-10-06 | セプラコア，インコーポレーテッド | Methods and compositions for the treatment of emesis, nausea and other disorders using optically pure R(+) ondansetron |
| FR2679451B1 (en) * | 1991-07-22 | 1994-09-09 | Prographarm Laboratoires | MULTIPARTICLE TABLET WITH RAPID DELIVERY. |
| CA2179382C (en) * | 1994-01-31 | 2009-11-10 | Takao Mizumoto | Intrabuccally dissolving compressed moldings and production process thereof |
| DE19637082A1 (en) * | 1996-09-12 | 1998-03-19 | Boehringer Mannheim Gmbh | Rapidly disintegrating pellets |
| GB9802201D0 (en) * | 1998-02-03 | 1998-04-01 | Cerestar Holding Bv | Free-flowable directly compressible starch as binder,disintegrant and filler for compresion tablets and hard gelatine capsules |
| DK1058538T3 (en) * | 1998-03-06 | 2002-10-21 | Eurand Int | Quickly disintegrating tablets |
| WO2000057857A1 (en) * | 1999-03-25 | 2000-10-05 | Yuhan Corporation | Rapidly disintegrable tablet for oral administration |
| GB9914936D0 (en) * | 1999-06-26 | 1999-08-25 | Cerestar Holding Bv | Directly compressible starch as enhancer of properties of excipients when used as binder and disintegrant for compression tablets |
| JP3435664B2 (en) * | 1999-12-08 | 2003-08-11 | ヤンセンファーマ株式会社 | Oral fast disintegrating tablet and method for producing the same |
| US6642276B2 (en) * | 2001-10-01 | 2003-11-04 | M/S Ind-Swift Limited | Controlled release macrolide pharmaceutical formulations |
| US6827946B2 (en) * | 2001-12-05 | 2004-12-07 | Collegium Pharmaceutical, Inc. | Compositions containing both sedative and non-sedative antihistamines |
| NZ534340A (en) * | 2002-02-07 | 2006-04-28 | Pharmacia Corp | Pharmaceutical dosage form for mucosal delivery |
| JP2005015477A (en) * | 2003-06-06 | 2005-01-20 | Takeda Chem Ind Ltd | Solid formulation |
| US8545881B2 (en) * | 2004-04-19 | 2013-10-01 | Eurand Pharmaceuticals, Ltd. | Orally disintegrating tablets and methods of manufacture |
-
2006
- 2006-02-06 WO PCT/JP2006/301951 patent/WO2006085497A1/en not_active Application Discontinuation
- 2006-02-06 JP JP2007502589A patent/JP5004236B2/en not_active Expired - Fee Related
-
2012
- 2012-02-23 JP JP2012037354A patent/JP5342028B2/en not_active Expired - Fee Related
-
2013
- 2013-09-04 JP JP2013182805A patent/JP2014001233A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001513545A (en) * | 1997-08-22 | 2001-09-04 | スミスクライン・ビーチャム・コーポレイション | Rapidly disintegrating methylcellulose tablets |
| JP2002524410A (en) * | 1998-09-08 | 2002-08-06 | スミスクライン・ビーチャム・コーポレイション | Lipstatin derivative-soluble fiber tablet |
| JP2000273039A (en) * | 1999-01-20 | 2000-10-03 | Taisho Pharmaceut Co Ltd | Composition disintegrable in oral cavity |
| WO2000047233A1 (en) * | 1999-02-15 | 2000-08-17 | Sumitomo Pharmaceuticals Co., Ltd. | Tablets quickly disintegrated in the oral cavity |
| JP2003055197A (en) * | 2001-06-07 | 2003-02-26 | Tanabe Seiyaku Co Ltd | Functional particle-containing intraoral disintegrative preparation |
| WO2003074029A1 (en) * | 2002-03-07 | 2003-09-12 | Vectura Limited | Fast melt multiparticulate formulations for oral delivery |
| JP2004002326A (en) * | 2002-03-22 | 2004-01-08 | Takeda Chem Ind Ltd | Rapidly disintegrating solid preparation |
| WO2004064810A1 (en) * | 2003-01-21 | 2004-08-05 | Nippon Shinyaku Co., Ltd. | Tablet quickly melting in oral cavity |
| JP2004315483A (en) * | 2003-02-28 | 2004-11-11 | Towa Yakuhin Kk | Orally disintegrating tablet |
| JP2008521808A (en) * | 2004-11-24 | 2008-06-26 | テバ ファーマシューティカル インダストリーズ リミティド | Rasagiline oral disintegrating composition |
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2006085497A1 (en) | 2008-06-26 |
| JP2014001233A (en) | 2014-01-09 |
| WO2006085497A1 (en) | 2006-08-17 |
| JP2012107049A (en) | 2012-06-07 |
| JP5342028B2 (en) | 2013-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5342028B2 (en) | Orally disintegrating tablets | |
| JP5693635B2 (en) | Orally disintegrating tablet masking bitterness and method for producing the same | |
| JP6092936B2 (en) | Method for producing orally disintegrating tablets | |
| JP5209492B2 (en) | Pharmaceutical formulations for the production of fast-disintegrating tablets | |
| JP5074190B2 (en) | Orally rapidly disintegrating tablets | |
| JP5332615B2 (en) | Orally disintegrating tablet and method for producing the same | |
| JP4920798B2 (en) | Intraoral quick disintegrating tablet containing two or more kinds of particles | |
| KR101386022B1 (en) | Quickly disintegrating tablet produced by direct dry-tabletting | |
| WO2005037319A1 (en) | Composition for tablet rapidly disintegrable in mouth | |
| WO2002069934A1 (en) | Preparations quickly disintegrating in oral cavity | |
| JP2001058944A (en) | Rapidly disintegrating solid formulation | |
| JP2003034655A (en) | Fast degradable solid tablet | |
| KR20100034057A (en) | Pranlukast hydrate-containing preparation having relieved bitterness | |
| JP5062872B2 (en) | Orally disintegrating tablets with reduced unpleasant taste | |
| JPWO2009054432A1 (en) | Oral rapidly disintegrating pharmaceutical composition and method for producing the same | |
| JP2002029964A (en) | Solid medicine composition | |
| JP5201837B2 (en) | Orally disintegrating tablets | |
| JP2002138055A (en) | Intraoral quick disintegration type compression molding and its production method | |
| JP2001131091A (en) | Additive for solid preparation | |
| JP2004107258A (en) | Compression molded hypnotic preparation | |
| WO1999055311A1 (en) | Tablets quickly disintegrated in oral cavity and process for producing the same | |
| JP2006232680A (en) | Disintegrator for tablet and tablet using the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090115 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090115 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120110 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120223 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120515 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120517 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150601 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5004236 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |